PROJECT SUMMARY Juvenile idiopathic arthritis-associated uveitis (JIA-U) is a chronic inflammatory eye disease that affects 20% of children with JIA and can lead to sight-threatening complications. Regular ophthalmic screening of children with JIA is crucial because early uveitis detection can prevent visual complications and influence therapeutic management. Our long-term goal is to prevent sight-threatening ocular damage in children with JIA-U by improving uveitis detection and treatment. This investigation is a multi-site longitudinal translational study that is a collaborative effort between experts in ophthalmology, rheumatology, proteomics, assay development, genetics, and biostatistics. The objectives of this study are to: 1) Delineate a biomarker profile in tears that identifies children at increased risk for JIA-U, 2) Identify genetic risk factors for early uveitis diagnosis among children with JIA, and 3) Develop a uveitis risk estimator integrating demographics, clinical factors, JIA-U biomarkers, and genetic variations. We will enroll 250 children with recently diagnosed JIA, without clinical evidence of uveitis, and follow them prospectively. Levels of biomarkers will be compared at serial time points in children with JIA-U and those who do not develop uveitis to understand the window of detection. We will also conduct SNP-based genetic association studies that include 750 children with JIA (no uveitis) and 750 with JIA-U to identify genetic variations that are related to biomarker levels and also to genetic predilection to eye disease. Using an integrative approach that considers clinical, biological, and genetic factors, we will generate a risk estimator for uveitis that will identify children at elevated risk for eye disease. We expect that application of this new tool early in disease will allow for early intervention and improved vision outcomes.